Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: The EPIC study

Laure Dossus, Susen Becker, Sabina Rinaldi, Annekatrin Lukanova, Anne Tjønneland, Anja Olsen, Kim Overvad, Nathalie Chabbert-Buffet, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Birgit Teucher, Jenny Chang-Claude, Tobias Pischon, Heiner Boeing, Antonia Trichopoulou, Vasiliki Benetou, Elisavet Valanou, Domenico Palli, Sabina Sieri, Rosario TuminoCarlotta Sacerdote, Rocco Galasso, Maria Luísa Redondo, Catalina Bonet Bonet, Esther Molina-Montes, Jone M. Altzibar, Maria Dolores Chirlaque, Eva Ardanaz, H. Bas Bueno-De-Mesquita, Fränzel J B Van Duijnhoven, Petra H M Peeters, N. Charlotte Onland-Moret, Eva Lundin, Annika Idahl, Kay Tee Khaw, Nicholas Wareham, Naomi Allen, Isabelle Romieu, Veronika Fedirko, Pierre Hainaut, Dora Romaguera, Teresa Norat, Elio Riboli, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, P trend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.

Original languageEnglish
Pages (from-to)2032-2037
Number of pages6
JournalInternational Journal of Cancer
Volume129
Issue number8
DOIs
Publication statusPublished - Oct 15 2011

Keywords

  • endometrial cancer
  • inflammation
  • prospective
  • soluble TNF receptors
  • tumor necrosis factor (TNF)-α

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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